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Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder Symptoms in Youths With a History of Mild Traumatic Brain Injury

  • Sonja Stojanovski
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada

    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
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  • Daniel Felsky
    Affiliations
    Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York

    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts
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  • Joseph D. Viviano
    Affiliations
    Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Saba Shahab
    Affiliations
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Rutwik Bangali
    Affiliations
    Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Christie L. Burton
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada
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  • Gabriel A. Devenyi
    Affiliations
    Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada

    Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Lauren J. O’Donnell
    Affiliations
    Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
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  • Peter Szatmari
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • M. Mallar Chakravarty
    Affiliations
    Cerebral Imaging Centre, Douglas Institute, Montreal, Quebec, Canada

    Department of Biomedical Engineering, McGill University, Montreal, Quebec, Canada

    Department of Psychiatry, McGill University, Montreal, Quebec, Canada
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  • Stephanie Ameis
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Russell Schachar
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
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  • Aristotle N. Voineskos
    Affiliations
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
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  • Anne L. Wheeler
    Correspondence
    Address correspondence to Anne L. Wheeler, Ph.D., Hospital for Sick Children, SickKids Research Institute, 686 Bay St., Toronto, Ontario M5G 0A4, Canada.
    Affiliations
    Neuroscience and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada

    Department of Physiology, University of Toronto, Toronto, Ontario, Canada
    Search for articles by this author

      Abstract

      Background

      Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of traumatic brain injury (TBI) in youths. The objective of this study was to examine whether ADHD symptoms are differentially associated with genetic risk and brain structure in youths with and without a history of TBI.

      Methods

      Medical history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a community sample of youths. ADHD symptom severity was compared between those with and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history, genetic vulnerability, brain structure, and ADHD symptoms was examined by assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the corpus callosum and corona radiata.

      Results

      Youths with TBI reported greater ADHD symptom severity compared with those without TBI. Polygenic score was positively associated with ADHD symptoms in youths without TBI but not in youths with TBI. The negative association between the caudate volume and ADHD symptoms was not moderated by a history of TBI. However, the relationship between ADHD symptoms and structure of the genu of the corpus callosum was negative in youths with TBI and positive in youths without TBI.

      Conclusions

      The identification of distinct ADHD etiology in youths with TBI provides neurobiological insight into the clinical heterogeneity in the disorder. Results indicate that genetic predisposition to ADHD does not increase the risk for ADHD symptoms associated with TBI. ADHD symptoms associated with TBI may be a result of a mechanical insult rather than neurodevelopmental factors.

      Keywords

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